Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response genes

• Published in: Digestive diseases and sciences Vol. 43; no. 7; pp. 1526 - 1536
• Main Authors: TAPPENDEN, K. A, MCBURNEY, M. I
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Heidelberg Springer 01.07.1998; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Blotting, Northern; Blotting, Western; Digestive System - drug effects; Digestive System - metabolism; Fatty Acids, Volatile - administration & dosage; Fatty Acids, Volatile - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Hormones - metabolism; Gene Expression; Glucagon - metabolism; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Male; Medical sciences; Other diseases. Semiology; Parenteral Nutrition, Total; Peptides - metabolism; Proglucagon; Protein Precursors - metabolism; Proto-Oncogenes - genetics; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Immunopathology; Short chain; Immune response; Rat; Rodentia; Lipids; Experimental study; Gene expression; Gastrointestinal; Fatty acids; Vertebrata; Mammalia; Animal; Digestive diseases; Molecular biology; Adaptation
• DOI: 10.1023/A:1018819032620
• ISSN: 0163-2116

Luminal and systemic short chain fatty acids (SCFA) stimulate mucosal proliferation but the mechanism(s) is unclear. This study examined acute effects of systemic SCFAs on gastrointestinal structure and function and signals potentially mediating SCFA-induced mucosal proliferation. Male Sprague-Dawley rats (246+/-2 g) received nutrients as either standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous formulation containing SCFAs (TPN + SCFA). Animals were randomized to one of five treatments: standard TPN for 72 hr, TPN + SCFA for 72 hr, or standard TPN followed by TPN + SCFA for the final 6, 12, and 24 hr. SCFAs reduced (P < 0.003) ileal protein within 6 hr. Jejunal GLUT2 expression was increased (P=0.0001) in all SCFA groups and ileal GLUT2 protein in the 6-, 12-, and 24-hr SCFA groups (P < 0.05). SCFAs increased (P < 0.003) ileal proglucagon abundance following 6, 12, and 24 hr, and plasma GLP-2 concentration following 12 hr (P < 0.03). Jejunal c-myc expression was increased (P < 0.001) following 6, 12, and 24 hr of SCFAs. SCFAs increased ileal c-myc, c-jun, and c-fos expression following 24 hr (P < 0.02), 12 hr (P < 0.05) and 6, 12, and 24 hr (P=0.0001), respectively. In conclusion, systemic SCFAs increase plasma GLP-2 and ileal proglucagon mRNA, GLUT2 expression and protein, and c-myc, c-jun, and c-fos expression.